Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Abstract Background Oxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2. Results Experiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: received a basal diet (control) and diets supplemented with 0.15%, 0.30% and 0.45% PQQ, respectively. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0–28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, Occludin and Claudin-1; and decreased ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. Conclusions PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.

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Pyrroloquinoline quinone regulates the redox status in vitro and vivo of weaned pigs via the Nrf2/HO-1 pathway

10.21203/rs.3.rs-135680/v2 ◽

2021 ◽

Author(s):

Caiyun Huang ◽

Zijuan Fan ◽

Dandan Han ◽

Lee J Johnston ◽

Xi Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Antioxidant Properties ◽

Redox Status ◽

Pyrroloquinoline Quinone ◽

Feed Ratio ◽

Weaned Pigs ◽

Positive Effects ◽

Diarrhea Incidence

Abstract Background: Oxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2.Results: Experiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: received a basal diet (control) and diets supplemented with 0.15, 0.30, and 0.45 % PQQ. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0-28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, occludin and claudin-1; and decreased ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. Conclusions: PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.

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Pyrroloquinoline Quinone Regulates the Redox Status in Vitro and Vivo of Weaned Pigs via the Nrf2/HO-1 Pathway

10.21203/rs.3.rs-135680/v1 ◽

2020 ◽

Author(s):

Caiyun Huang ◽

Zijuan Fan ◽

Dandan Han ◽

Lee J Johnston ◽

Xi Ma ◽

...

Keyword(s):

Cell Viability ◽

Average Daily Gain ◽

Antioxidant Properties ◽

Redox Status ◽

Pyrroloquinoline Quinone ◽

Feed Ratio ◽

Weaned Pigs ◽

Positive Effects ◽

Diarrhea Incidence

Abstract BackgroundOxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2.ResultsExperiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: receiving a basal diet (control) and diets supplemented with 0.15, 0.30, and 0.45 % PQQ. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0-28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, occludin and claudin-1; and decrease ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. ConclusionsPQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.

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Inhibitory effects of Panax ginseng glycoproteins in models of doxorubicin-induced cardiac toxicity in vivo and in vitro

Food & Function ◽

10.1039/d1fo01307f ◽

2021 ◽

Author(s):

Yajun Chen ◽

Lei Wang ◽

Tianjia Liu ◽

Zhidong Qiu ◽

Ye Qiu ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Panax Ginseng ◽

Cardiac Toxicity ◽

H9c2 Cell ◽

Inhibitory Effects ◽

Myocardial Oxidative Stress

We investigated the protective effect of PGP against DOX-induced cardiotoxicity in vitro and in vivo. PGP increases H9C2 cell viability and inhibits apoptosis, alleviating DOX-induced myocardial oxidative stress-related cardiotoxicity.

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Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction

AJP Cell Physiology ◽

10.1152/ajpcell.00045.2009 ◽

2009 ◽

Vol 297 (4) ◽

pp. C928-C934 ◽

Cited By ~ 23

Author(s):

Changgong Wu ◽

Lin Yan ◽

Christophe Depre ◽

Sunil K. Dhar ◽

You-Tang Shen ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Heart Failure ◽

Cytochrome C ◽

Protein Expression ◽

Cell Viability ◽

Cytochrome C Oxidase ◽

Mitochondrial Gene

Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF ( P < 0.05 vs. sham), whereas COX II expression remained unchanged. COX III protein expression increased 5-fold after MI and further increased 10-fold after HF compared with sham ( P < 0.05 vs. sham). The physiological impact of COX III regulation was examined in vitro. Overexpression of COX III in mitochondria of HL-1 cells resulted in an 80% decrease in COX I, 60% decrease in global COX activity, 60% decrease in cell viability, and threefold increase in apoptosis ( P < 0.05). Oxidative stress induced by H2O2 significantly ( P < 0.05) increased COX III expression. H2O2 decreased cell viability by 47 ± 3% upon overexpression of COX III, but only by 12 ± 5% in control conditions ( P < 0.05). We conclude that ischemic stress in vivo and oxidative stress in vitro lead to upregulation of COX III, followed by downregulation of COX I expression, impaired COX oxidative activity, and increased apoptosis. Therefore, upregulation of COX III may contribute to the increased susceptibility to apoptosis following MI and subsequent HF.

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Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

Journal of Toxicology ◽

10.1155/2011/109516 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Victor Paromov ◽

Sudha Kumari ◽

Marianne Brannon ◽

Naga S. Kanaparthy ◽

Hongsong Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Sulfur Mustard ◽

Alkylating Agents ◽

Water Soluble ◽

Model Systems ◽

Mustard Gas

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated usingin vitromodel systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously describedin vivoprotective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

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Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7956158 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 19

Author(s):

Fujie Yan ◽

Yushu Chen ◽

Ramila Azat ◽

Xiaodong Zheng

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Hepg2 Cells ◽

Insulin Signalling ◽

Glucose Consumption ◽

Redox Status ◽

C Elegans ◽

Beneficial Effects

Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation. In vivo, extended lifespan was observed in C. elegans damaged by paraquat in the presence of MAE, while these beneficial effects were disappeared in pmk-1 and daf-16 mutants. PMK-1 and SKN-1 were activated after exposure to paraquat and MAE suppressed PMK-1 activation but enhanced SKN-1 stimulation. Our findings suggested that MAE recovered redox status in HepG2 cells and C. elegans that suffered from oxidative stress, which might be by targeting MAPKs and Nrf2.

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Targeted Delivery of Intranasally Administered Cyclovirobuxine D Liposomes to Brain for Treatment Cerebral Ischemia-Reperfusion Injury via Anti-oxidative Stress and Activating Autophagy

10.21203/rs.3.rs-966870/v2 ◽

2022 ◽

Author(s):

Tuo Liu ◽

Fang Yang ◽

Xiangyi Lu ◽

Chang Liu ◽

Yang Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Protein Expressions ◽

Cerebral Ischemia Reperfusion Injury ◽

Ht22 Cell

Abstract The lack of effective therapy mandates development of treatment for cerebral ischemia-reperfusion injury (CIRI. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study focused on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. In order to evaluate these, the CIRI rat model was induced by middle cerebral artery occlusion (MCAO)-reperfusion. Pharmacological evaluation was assessed in vivo by general indexs, neurobehavioral scores, triphenyl tetrazolium chloride (TTC) staining, histopathological staining (HE staining and Nissl staining), small animal magnetic resonance imaging, biochemical assay and Western blot. The results show that CVBD liposomes alleviated pathological damage of brain. Futhermore, the protective effect of CVBD liposomes on OGD/R-injured HT22 cell was investigated by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions (LC3, p62 and Beclin 1) were analyzed by Western blot. Meanwhile, the classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulated mechanism of CVBD brain-targeted liposomes in treating CIRI. In cell model of oxygen and glucose deprivation/re-oxygenation, CVBD liposomes increased cell viability and decreased ROS level. CVBD liposomes improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated to anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro, showing a great potential in treating CIRI in clinic.

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miR-141 mediates recovery from acute kidney injury

Scientific Reports ◽

10.1038/s41598-021-94984-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lucy J. Newbury ◽

Kate Simpson ◽

Usman Khalid ◽

Imogen John ◽

Lluís Bailach de Rivera ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Cell Viability ◽

Messenger Rna ◽

Tyrosine Phosphatase ◽

Kidney Injury ◽

Clinical Problem ◽

Proximal Tubular

AbstractAcute kidney injury (AKI) is a global clinical problem characterised by a sudden decline in renal function and mortality as high as 60%. Current AKI biomarkers have limited ability to classify disease progression and identify underlying pathological mechanisms. Here we hypothesised that alterations in urinary microRNA profiles could predict AKI recovery/nonrecovery after 90 days, and that injury-specific changes would signify microRNA mediators of AKI pathology. Comparison of urinary microRNA profiles from AKI patients with controls detected significant injury-specific increases in miR-21, miR-126 and miR-141 (p < 0.05) and decreases in miR-192 (p < 0.001) and miR-204 (p < 0.05). Expression of miR-141 increased in renal proximal tubular epithelial cells (PTECs) under oxidative stress in vitro and unilateral ischaemic reperfusion injury in vivo. Forced miR-141 expression in the presence of H2O2 increased PTEC death and decreased cell viability. Of nine messenger RNA targets with two or more miR-141 3’-untranslated region binding sites, we confirmed protein tyrosine phosphatase receptor type G (PTPRG) as a direct miR-141 target in PTECs. PTPRG-specific siRNA knockdown under oxidative stress increased PTEC death and decreased cell viability. In conclusion, we detected significant alterations in five urinary microRNAs following AKI, and identified proximal tubular cell PTPRG as a putative novel therapeutic target.

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The Antioxidant Effects of a Polyphenol-Rich Grape Pomace ExtractIn VitroDo Not CorrespondIn VivoUsing Exercise as an Oxidant Stimulus

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/185867 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 37

Author(s):

Aristidis S. Veskoukis ◽

Antonios Kyparos ◽

Michalis G. Nikolaidis ◽

Dimitrios Stagos ◽

Nektarios Aligiannis ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Hydroxyl Radicals ◽

Antioxidant Properties ◽

Redox Status ◽

Grape Pomace ◽

Antioxidant Effects ◽

Essential Food

Fruits, such as grapes, are essential food of the Mediterranean diet. Grape extracts have potent antioxidant and chemopreventive propertiesin vitro. Numerous studies have examined the effects of plant extract administration on redox status at rest in animals and humans but their results are controversial. However, there are no studies comparing thein vitroandin vivoeffects of plant extracts on oxidative stress using exercise as an oxidant stimulus. Thus, the aim of this study was to investigate whether a polyphenol-rich grape pomace extract of theVitis viniferaspecies possessesin vitroantioxidant properties and to examine whether these properties apply in anin vivomodel at rest and during exercise. Our findings indicate that the tested extract exhibits potentin vitroantioxidant properties because it scavenges the DPPH•and ABTS•+radicals and inhibits DNA damage induced by peroxyl and hydroxyl radicals. Administration of the extract in rats generally induced oxidative stress at rest and after exercise whereas exercise performance was not affected. Our findings suggest that the grape pomace extract does not behave with the same wayin vitroandin vivo.

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Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress

Stem Cells International ◽

10.1155/2020/2560828 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Sung-Chan Shin ◽

Hyung-Sik Kim ◽

Yoojin Seo ◽

Cho Hee Kim ◽

Ji Min Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Viability ◽

Vocal Fold ◽

Vocal Folds ◽

Dependent Manner ◽

The Impact

The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) has been proved in several in vitro and in vivo models based on their antioxidative capacity. Oxidative stress is involved in the formation of vocal fold scars and the aging of vocal folds. However, few studies have examined the direct correlation between oxidative damage and reconstitution of extracellular matrix (ECM) in the vocal fold fibrosis. We, therefore, sought to investigate the impact of oxidative stress on cell survival and ECM production of human vocal fibroblasts (hVFFs) and the protective effects elicited by TMSCs against oxidative damages in hVFFs. hVFFs were exposed to different concentrations of tert-butyl hydroperoxide in the presence or absence of TMSCs. Cell viability and reactive oxygen species (ROS) production were assessed to examine the progression of oxidative stress in vitro. In addition, expression patterns of ECM-associated factors including various collagens were examined by real-time PCR and immunocytochemical analysis. We found that both cell viability and proliferation capacity of hVFFs were decreased following the exposure to tBHP in a dose-dependent manner. Furthermore, tBHP treatment induced the generation of ROS and reactive aldehydes, while it decreased endogenous activity of antioxidant enzymes in hVFF. Importantly, TMSCs could rescue these oxidative stress-associated damages of hVFFs. TMSCs also downregulated tBHP-mediated production of proinflammatory cytokines in hVFFs. In addition, coculture with TMSC could restore the endogenous matrix metalloproteinase (MMP) activity of hVFFs upon tBHP treatment and, in turn, reduce the oxidative stress-induced ECM accumulation in hVFFs. We have, therefore, shown that the changes in hVFF proliferative capacity and ECM gene expression induced by oxidative stress are consistent with in vivo phenotypes observed in aging vocal folds and vocal fold scarring and that TMSCs may function to reduce oxidative stress in aging vocal folds.

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